A Study to Test Whether Different Doses of Alteplase Help People With Severe Breathing Problems Because of COVID-19

Inclusion Criteria:

• Age ≥ 18 years (or above legal age, e.g. UK ≥16 years)
• ARDS with PaO2*/FiO2 ratio >100 and ≤300, either on non-invasive ventilator support,OR on mechanical ventilation (<48 hours since intubation),
• with bilateral opacities in chest X-ray or CT scan (not fully explained byeffusions, lobar/lung collapse, or nodules)
• with respiratory failure (not fully explained by cardiac failure/fluid overload) (*or estimation of PaO2/FiO2 from pulse oximetry (SpO2/FiO2))
• SARS-CoV-2 positive (laboratory-confirmed reverse transcription polymerase chainreaction (RT PCR) test)
• Fibrinogen level ≥ lower limit of normal (according to local laboratory)
• D-Dimer ≥ upper limit of normal (ULN) according to local laboratory
• Signed and dated written informed consent in accordance with ICH Good ClinicalPractice (GCP) and local legislation prior to admission to the Trial

Exclusion Criteria:

• Massive confirmed pulmonary embolism (PE) with haemodynamic instability at trialentry, or any (suspected or confirmed) PE that is expected to require therapeuticdosages of anticoagulants during the treatment period
• Indication for therapeutic dosages of anticoagulants at trial entry
• Patients on mechanical ventilation for longer than 48 hours
• Chronic pulmonary disease i.e. with known forced expiratory volume in 1 second (FEV1) <50%, requiring home oxygen, or oral steroid therapy or hospitalisation forexacerbation within 12 months, or significant chronic pulmonary disease in theInvestigator's opinion, or primary pulmonary arterial hypertension
• Has a Do-Not-Intubate (DNI) or Do-Not-Resuscitate (DNR) order
• In the opinion of the investigator not expected to survive for > 48 hours afteradmission
• Planned interventions during the first 5 days after randomisation, such as surgery,insertion of central catheter or arterial line, drains, etc.
• Patients with known hypersensitivity to the active substance alteplase, gentamicin (atrace residue from the manufacturing process) or to any of the excipients
• Significant bleeding disorder at present or within the past 3 months, knownhaemorrhagic diathesis
• Patients receiving effective oral anticoagulant treatment, e.g. vitamin K antagonistswith International normalised ratio (INR) >1.3, or any direct oral anticoagulantwithin the past 48 hours Further exclusion criteria apply.